Vector-Borne Disease Research

at Tulane

SPHU-1020

Dawn Wesson, PhD

Department of Tropical Medicine

Overview

• Introduction

• General Concepts: vectors, types of vector-borne transmission, vector incrimination, zoonoses, surveillance

• Specific Pathogen-Arthropod-Vertebrate Transmission Cycles: dengue virus, West Nile virus, American trypanosomiasis (Chagas disease)

Introduction

• Training for VBD research

• VBD at Tulane (dengue, WNV, malaria, chikungunya, Chagas dz, Lyme dz)

• Local vs. International research

• Funding sources (NIH, NSF, BMGF, BORSF, etc.)

How do we define a vector?

An arthropod* responsible for transmission of parasites among vertebrate hosts.

* Arthropods include insects (mosquitoes, tsetse flies, sandflies, blackflies, lice, fleas, kissing bugs) and arachnids (mites, ticks, spiders and scorpions).

Aedes aegypti

Dengue and Yellow Fever viruses

Culex quinquefasciatus

Filariasis, West Nile & other viruses

Anopheles gambiae

Malaria

Major mosquito-borne diseases and the most important mosquito vector species

Tsetse fly – African Sleeping SicknessSandfly - Leishmaniasis

Kissing bug – Chagas Disease Blackfly - Onchocerciasis

Flea - Plague

Tick – Lyme Disease, Crimean-Congo Hemorrhagic Fever

Body louse – Epidemic TyphusHorse fly – Tularemia

Types of Vector-Borne Transmission

Mechanical Transmission – simplest form

(not necessary for pathogen survival – “flying/crawling hypodermic needle” phenomenon)

Biological Transmission – more complex

(necessary for pathogen survival – results in amplification or development in vector)

General Types of Biological Transmission

Vertical

Horizontal

Vertical Transmission

Trans-stadial(ticks, kissing bugs)

Trans-generational Transovarial – female to progeny, including males

(mosquitoes, ticks)

Horizontal Transmission

Bite (saliva or gut infection)(malaria, dengue, filariasis, etc.)

Feces(Chagas disease)

Crushing Infected Arthropod

(epidemic typhus, etc.)

Horizontal Transmission Types

Multiplicative (Propagative)(increase in number - Dengue)

Developmental

(change stage - Filariasis)

Cyclopropagative

(change stage and increase in number - Malaria)

Pathogen Infection in Arthropods

Extrinsic Incubation Period - EIP

Time interval between vector infection and potential for pathogen transmission to

vertebrate host (determined by controlled experimental studies)

If vector dies (is killed) before EIP is completed, transmission will not occur.

Ecological Parameters Affecting Vector Populations:

Availability of food (What do they eat, and when?)

Space (Where do they occur, and when?)

Water (Is their appearance seasonal – wet/dry?)

Temperature (Is their appearance seasonal – warm/cold?)

Predation ( Can we enhance or introduce predators to control them?)

Disease ( Can we identify pathogens to control them?)

Vector Incrimination

• Demonstrate an association in time and space between arthropod and disease

• Demonstrate direct contact between the arthropod and humans

• Demonstrate natural occurrence of the infectious agent in the insect

• Demonstrate “transmission” of the agent by the insect (laboratory-based vector competence)

How are these pathogen transmission parameters determined?

Laboratory Experimentation

(vector competence, EIP)

Field Surveillance

(temporal and spatial association between pathogen, vector and humans; other factors affecting disease prevention – insecticide or

antibiotic resistance)

Mosquito Life Cycle

Why is understanding vector life cycle important?

Highlighted Transmission Cycles

Mosquito-borne pathogens - arboviruses (dengue and West Nile virus)

Bug-transmitted pathogens – Chagas disease

Specific Pathogen-Arthropod-Vertebrate Transmission Cycles

Arboviruses: ARthropod-BOrne VIRUSES

• Dengue viruses 1-4 – dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)

• West Nile virus - West Nile fever and WN neuroinvasive disease (encephalitis, meningitis, etc.)

different vertebrate hosts and mosquito vectors

different transmission ecology

different control approaches

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Worldwide dengue distribution, early 2012.

Dengue Viruses

• 40% of the world’s population is at risk for dengue infection

• Each serotype provides specific lifetime immunity, and short-term cross-immunity

• All serotypes can cause severe and fatal disease

• Genetic variation within serotypes

Aedes aegypti

• Dengue transmitted by female mosquitoes between humans

• Primarily a daytime feeder

• Lives in and around human habitation

• Prefers to take blood from humans

• Lays eggs and produces larvae preferentially in artificial containers

Aedes albopictusAedes aegypti

Yellow Fever mosquito Asian Tiger mosquito

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25

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West Nile Neuroinvasive Disease (NID) in the United States, 1999 - 2012

Year WNV NID Deaths Mortality Rate

1999 59 7 11.9%

2000 19 2 10.5%

2001 64 9 14.1%

2002 2,946 284 9.6%

2003 2,860 264 9.2%

2004 1,142 100 8.8%

2005 1,294 119 9.2%

2006 1,459 177 12.1%

2007 1,217 124 10.2%

2008 687 44 6.4%

2009 335 30 9.0%

2010 601 45 7.5%

2011 486 46 9.5%

2012 2,734 243 8.9%

Total 15,903 1,494 9.4%

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West Nile virus (WNV) activity reported to ArboNET, by state, United States, 2012 (as of Dec. 11, 2012)

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West Nile virus (WNV) Neuroinvasive Disease Incidence reported to ArboNET, by county, United States, 2012 (as of Dec. 11, 2012)

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• At least 326 bird species have been reported to CDC's West Nile Virus avian mortality database from 1999-present.

• At least 60 species of mosquitoes have been found naturally infected with West Nile virus since 1999.

• 40% of unvaccinated equines will die from WNV infection.

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+++Ae. japonicus

++Cx. nigripalpus

+++Cx. tarsalis

+++Cx. salinarius

+++Cx. restuans

+++Ae. albopictus

++Cx. pipiens

+++Ae. atropalpus

Vector Competence

Species

+Ae. vexans

++Ae. triseriatus

++Ae. sollicitans

++Cx. quinquefasciatus

+Cq. perturbans

++Ae. taeniorhynchus

+Ae. cantator

+Ae. canadensis

Vector Competence

Species

Relative Vector Competence (Laboratory)

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Chagas Disease(American Trypanosomiasis)

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Chagas’ Disease - General

• Trypanosoma cruzi, the causative agent of Chagas disease, infects 8–11 million people.

• Triatomine bugs transmit Trypanosoma cruzi while feeding on vertebrate host; pathogen defecated in feces while bug feeds - host scratches infective feces into site of bite or into mucous membrane (eyes, etc.)

• Any triatomine bug can support development of T. cruzi, but differing environmental conditions enhance or suppress transmission to humans

• Important vectors: Triatoma infestans, Rhodnius prolixus, Panstrongylus megistus, T. dimidiata

Plague ControlChagas Disease

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Non-human reservoirs for Chagas disease

Armadillo

Opossum

Also, rats and mice, squirrels, raccoons, skunks, carnivores, monkeys, and domestic pets.

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Migration routes from Latin America and estimation of the total number of infected individuals in non-endemic countries.

Nature, 2010

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Chagas in the United States

• In the United States, the disease exists almost exclusively as a zoonosis.

• Only six autochthonous insect-borne cases have been reported in humans. The most recent was documented in New Orleans in 2006.

• The distribution of Chagas disease in the United States includes approximately the southern half of the country.

• Twelve species of triatomines are known to occur in the United States, the most important being Triatoma sanguisuga in the eastern United States, Triatoma gerstaeckeri in the region of Texas and New Mexico, and Triatoma rubida and Triatoma protracta in Arizona and California .

37Triatoma infestans

Rhodnius prolixus

Nature, 2010

Triatomine bugs transmitting Chagas disease feed at night, and pass the parasite to new hosts via fecal contamination.

Poor house construction contributes to transmission. Fumigation and home improvement are two successful control methods.

Careers in VBD

• Research (academic, industry)

• Vector control programs (municipal)

• Pest control operator (industry)

• International, national, regional, state level surveillance, epidemiology, policy

• Monitoring and assessment

• NGO’s

• Funding agencies